A primary goal of this laboratory is to increase our understanding of how growth factor-dependent cells escape the control of regulatory growth factors thus becoming autonomous tumor cells. One example of this process is the murine myeloma model. Previous studies by R. Nordan identified and characterized a cytokine, interleukin 6 (IL6), that supported the growth of early murine plasma cell tumors. These early tumors also require an inflammatory peritoneal oil granuloma for in vivo growth. Without this microenvironment, the cells fail to grow in vivo. The eventual progression of these tumors to a fully malignant phenotype in vivo is associated with a concomitant transition to IL6-independent growth in vitro. Our working hypothesis is that the early tumor cells require IL6 (supplied by the local microenvironment) for in vivo growth with the subsequent loss of IL6- dependence representing a key step in the progression to a fully malignant tumor. Since the establishment of this laboratory in the Tumor Biology Section in January, 1989, we have performed studies aimed at (1) elucidating the role of U,6 in the growth of human and murine tumor cells and (2) analyzing the mechanisms utilized by these cells escape the requirement for this growth factor. Although initially focusing on myeloma, we have also expanded our studies to other tumors as well.